title: Surface-mediated bone tissue morphogenesis from tunable nanolayered implant coatings.
abstract: The functional success of a biomedical implant critically depends on its stable bonding with the host tissue. Aseptic implant loosening accounts for more than half of all joint replacement failures. Various materials, including metals and plastic, confer mechanical integrity to the device, but often these materials are not suitable for direct integration with the host tissue, which leads to implant loosening and patient morbidity. We describe a self-assembled, osteogenic, polymer-based conformal coating that promotes stable mechanical fixation of an implant in a surrogate rodent model. A single modular, polymer-based multilayered coating was deposited using a water-based layer-by-layer approach, by which each element was introduced on the surface in nanoscale layers. Osteoconductive hydroxyapatite (HAP) and osteoinductive bone morphogenetic protein-2 (BMP-2) contained within the nanostructured coating acted synergistically to induce osteoblastic differentiation of endogenous progenitor cells within the bone marrow, without indications of a foreign body response. The tuned release of BMP-2, controlled by a hydrolytically degradable poly(β-amino ester), was essential for tissue regeneration, and in the presence of HAP, the modular coating encouraged the direct deposition of highly cohesive trabecular bone on the implant surface. In vivo, the bone-implant interfacial tensile strength was significantly higher than standard bioactive bone cement, did not fracture at the interface, and had long-term stability. Collectively, these results suggest that the multilayered coating system promotes biological fixation of orthopedic and dental implants to improve surgical outcomes by preventing loosening and premature failure.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Nisarg J
authors.initials: NJ
authors.lastname: Shah
authors.forename: Md Nasim
authors.initials: MN
authors.lastname: Hyder
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Moskowitz
authors.forename: Mohiuddin A
authors.initials: MA
authors.lastname: Quadir
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Morton
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Seeherman
authors.forename: Robert F
authors.initials: RF
authors.lastname: Padera
authors.forename: Myron
authors.initials: M
authors.lastname: Spector
authors.forename: Paula T
authors.initials: PT
authors.lastname: Hammond
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000494:pharmacology; D001861:Bone Regeneration / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000737:chemistry* / Q000494:pharmacology; D017886:Durapatite / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D010012:Osteogenesis / Q000187:drug effects; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology; D019736:Prostheses and Implants; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D055396:Bone Morphogenetic Protein 2; D020099:Coated Materials, Biocompatible; D011108:Polymers; D017886:Durapatite